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Receptor for advanced glycation end products contributes to microglial migration and amyloid beta-induced neurotoxicity. The receptor for advanced glycation end products (RAGE) is a receptor for multiple ligands, including amyloid beta (A beta), which is involved in the pathogenesis of Alzheimer's disease (AD). Because A beta-induced microglial migration has been implicated in the pathogenesis of AD, we determined whether RAGE is also involved in A beta-induced microglial migration. A beta-induced migration of microglial cells was evaluated by a modified Boyden chamber assay and quantified by the number of migrated cells per microscopic field. RAGE protein was detectable by Western blotting in cultured microglial cells. A beta-induced migration of microglial cells was attenuated by treatment with a peptide inhibitor of RAGE (BAY 11-7082), and RAGE protein expression was up-regulated in microglia treated with A beta. Immunocytochemistry revealed that RAGE was expressed in microglia in the pial vessels of the mouse brain, and up-regulation of RAGE was observed in microglia near amyloid plaques. In an in vivo model of the mouse brain, intracerebroventricular injection of A beta induced microglial migration and RAGE up-regulation, which was inhibited by BAY 11-7082. BAY 11-7082 also reduced A beta-induced neuronal death in the presence of microglia. These results suggest that RAGE contributes to A beta-induced microglial migration in AD pathology, and RAGE may play a role in microglial neurotoxicity.The present invention is directed to a novel apparatus for the continuous casting of molten metal, particularly aluminum, and more particularly to a continuous casting wheel having an inlet for receiving molten metal and an exit for casting the metal into a mold. The cast metal is kept at a uniform temperature to avoid warping or other distortion of the cast metal. Conventional continuous casting wheels employ a solid circular casting wheel having a mold receiving inlet and casting outlet formed thereon. The wheel is rotated about a vertical axis and is immersed in a pool of molten metal, usually copper. The molten metal is introduced into the inlet of the wheel and is continuously discharged into the mold receiving in the casting wheel. In the past, the casting wheel has had a solid metal wheel cover which engages the outer periphery of the casting wheel to stabilize it









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